CASE REPORT Open Access

Peritonitis due to Mycobacterium abscessusin peritoneal dialysis patients: casepresentation and mini-reviewErina Ono1, Eiichiro Uchino1, Keita P. Mori1,2*, Hideki Yokoi1, Naohiro Toda1, Kenichi Koga3, Masato Kasahara4,Takeshi Matsubara1 and Motoko Yanagita1,2

Abstract

Background: Peritoneal dialysis (PD)-associated peritonitis caused by nontuberculous mycobacteria (NTM), includingMycobacterium abscessus (M. abscessus), is a rare but serious complication that forces PD to be withdrawn. Several casesof peritonitis by NTM have been reported, and optimal treatment has not yet been established.

Case presentations: We report two cases of PD-associated peritonitis caused by M. abscessus. In both cases, peritonitisdeveloped after an exit-site infection. The patients did not have any typical signs of peritonitis or an elevated nucleatedcell count of the dialysis effluent in the early phase. In addition, effluent cultures were negative at admission in bothcases, although M. abscessus was identified in effluent cultures in the late phase. One patient recovered after the PDcatheter was removed, and multi-antibiotic treatment was administered for 6 months. The other patient subsequentlydeveloped encapsulating peritoneal sclerosis (EPS) 16months after the onset of infection. In addition, the EPS wascomplicated by intestinal perforation into infected ascites. The infection resolved with antibiotic treatment andoctreotide administration to diminish bowel leakage into the infected cavity.

Conclusions: The combination of amikacin, clarithromycin, and imipenem/cilastatin with PD catheter removal may beeffective for the treatment of M. abscessus PD-associated peritonitis. The prognosis of M. abscessus-induced peritonitis isgenerally poor, and it is of note that residual encapsulated ascites in the peritoneal cavity after treatment may increasethe risk of infection recurrence or EPS development.

Keywords: Encapsulating peritoneal sclerosis, Exit-site infection, Mycobacterium abscessus, Nontuberculousmycobacteria, Peritoneal dialysis, Peritonitis

BackgroundPeritoneal dialysis (PD) is a standard modality of renalreplacement therapy for end-stage renal disease (ESRD).Clinicians, however, often encounter cases where PD isforced to be withdrawn as a result of factors such asperitonitis and volume overload. PD-associated peritonitisis one of the most significant complications caused by thecontamination of dialysate and spread of exit-site infection(ESI) or tunnel infection. Although PD-associated periton-itis is typically caused by bacteria such as coagulase-

negative staphylococcus and Staphylococcus aureus, whichcan be treated with antibiotics, an infection caused byacid-fast bacterial or fungal peritonitis requires PD catheterremoval in addition to the administration of multiple anti-bacterial drugs or antifungal drugs, respectively. Import-antly, the number of cases of peritonitis caused bynontuberculous mycobacteria (NTM), which are acid-fastbacilli, is increasing [1]. Mycobacterium abscessus (M.abscessus) is a species of rapidly growing NTM that existsin environments such as dirty water, soil, food, and animals[2]. Although M. abscessus is known to cause pulmonary,skin, and soft tissue infections, peritonitis caused by M.abscessus is reported to be rare [2, 3]. A recent reportshowed that antibiotics abuse could result in the spread ofM. abscessus infections [4]. Despite the rapid growth of M.

* Correspondence: moryk@kuhp.kyoto-u.ac.jp1Department of Nephrology, Graduate School of Medicine, Kyoto University,54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan2Medical Innovation Center, Graduate School of Medicine, Kyoto University,53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, JapanFull list of author information is available at the end of the article

© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Ono et al. Renal Replacement Therapy (2018) 4:52 https://doi.org/10.1186/s41100-018-0192-5

abscessus, it is difficult to diagnose and treat, especially atonset. Herein, we report two cases of peritonitis caused byM. abscessus and also review M. abscessus-associatedperitonitis in the literature.

Case presentationsCase 1A 59-year-old female had been receiving PD treatmentfor 1 year because of ESRD due to nephrosclerosis. Shehad no history of diabetes mellitus, immunodeficiency,mycobacterial infection, or peritonitis. She had not beentreated with immunosuppressants or anticancer drugs.Peritoneal equilibrium test (PET) showed high averagetransporter status 1 year before admission. She had beendiagnosed with ESI and tunnel infection 2 months beforeadmission. The gram stain and culture of the exit sitefor general bacteria were negative; acid-fast bacilli (AFB)stain was not performed. She was treated with surgicaldrainage, topical gentamicin, and systemic antibiotics byintravenous injection. Because she was unresponsive tothese treatments and the results of echographic examin-ation indicated that the infection was affecting the areafrom the exit site to the external cuff, but not to thecatheter tunnel between the internal and external cuff,we performed exit-site translocation. No improvement

in the skin infection was observed, however. She was ad-mitted to Kyoto University Hospital for further treatment.On admission, her body temperature was 36.4 °C, blood

pressure was 116/86mmHg, and heart rate was 89 beats/min. Her urine volume was 700mL/day, but the creatinineclearance was not measured. She had red, painful, andswollen wounds on the skin over the sites of the internalcuff, the external cuff, and the previously used externalcuff, with purulent discharge and ulceration (Fig. 1 A).There were no physical signs of peritonitis. Laboratory dataare summarized in Table 1. Her dialysis effluent was nor-mal in appearance, and her gram stain was negative(Table 1). Blood, sputum, and stool cultures were all nega-tive. Computed tomography (CT) showed no focal signs ofinflammation, except for increased density of subcutaneousfat around the PD catheter. She was diagnosed with refrac-tory ESI and tunnel infection. As her skin infection wasnot improved by the combination of intravenous cefazolinand ceftazidime, replacement of the PD catheter with de-bridement of the subcutaneous tissues around the catheterwas performed on the 5th day of admission. She developedfever and chills on the 11th day of admission, however, anddiarrhea, nausea, and vomiting on the 14th day ofadmission. As methicillin-resistant Staphylococcus aureus(MRSA) or Pseudomonas aeruginosa infection was sus-pected, we began intravenous cefepime and teicoplanin.

CEZ

CAZ

AZM

IPM/CS

CAM

AMK

CFPM

TEIC

TAZ/PIPC

A

B

Nucleated cell count of effluent (/µL) CRP (mg/dL)

30

20

10

0

Discharge

2000

1500

1000

500

a

Fig. 1 The clinical course of case 1. Horizontal axis indicates hospitalization. Bar graph indicates effluent nucleated cell count (black and gray barsrepresent ratios of neutrophils other than white blood cells, respectively). Line graph indicates the trend in serum C-reactive protein level. On the1st day of admission, the patient had red, painful, and swollen skin over the sites of the internal cuff, the external cuff, and the previously usedexternal cuff, with purulent discharge and ulceration (a). The dialysis effluent on the 25th day of admission was cloudy and bloody (b). The PDcatheter was removed on the 29th day of admission. The patient was discharged on the 77th day of admission. AMK, amikacin; AZM, azithromycin;CAM, clarithromycin; CAZ, ceftazidime; CEZ, cefazolin; CFPM, cefepime; CRP, C-reactive protein; IPM/CS, imipenem/cilastatin; PD, peritoneal dialysis;TAZ/PIPC, tazobactam/piperacillin; TEIC, teicoplanin

Ono et al. Renal Replacement Therapy (2018) 4:52 Page 2 of 10

On the 18th day of admission, the effluent became cloudywith fibrin precipitation and AFB was positive. The cultureof the internal cuff collected on the 1st day of admissionwas positive for M. abscessus. Her antibiotics were changedto oral azithromycin and intravenous imipenem/cilastatinbased on the results of antimicrobial susceptibility testing.Her renal replacement therapy was changed from PD tohemodialysis (HD). Although the inflammatory reactionwas improving, CT scan detected enhancement of the peri-toneum and an increased density of the mesentery. Thesefindings indicated the formation of adherent biofilm bybacteria in the second PD catheter. Although we suspectedencapsulating peritoneal sclerosis (EPS) because her efflu-ent was bloody and encapsulated ascites were detected byCT, we decided to remove the catheter to fully resolve theperitonitis on the 29th day of admission (Fig. 1 B).After removal, her symptoms and inflammatory reac-tion improved. Although encapsulated ascites remainedon the 44th day of admission (Fig. 3 A), they finallydisappeared after treatment. She was discharged on the77th day of admission with daily oral clarithromycinand intermittent intravenous amikacin and imipenem/cilastatin at each HD session (Fig. 1). After a total of 6months of antibiotics administration, she has had norecurrence of peritonitis or ileus and continues toundergo maintenance HD.

Case 2A 67-year-old male had been on PD for 5 years because ofESRD due to nephrosclerosis. He had no history of dia-betes mellitus, immunodeficiency, mycobacterial infection,or peritonitis. He had not been treated with immunosup-pressants or anticancer drugs. PET showed high averagetransporter status 6months before admission. He hadbeen diagnosed with ESI 6 months before admission dueto purulent discharge at the exit site. Gram stain and cul-ture of the exit site for general bacteria were negative, butAFB stain was not performed. His ESI improved with top-ical gentamicin. He had general malaise, anorexia, andcough beginning 2months before admission, however,and was nearly bedridden for the month prior to admis-sion due to his worsening symptoms. He was admitted toKyoto University Hospital for diarrhea, a 3.2-kg loss ofbody weight (previous mean body weight was 70 kg), andmild abdominal pain for 3 days.On admission, his body temperature was 37.4 °C,

blood pressure was 114/59 mmHg, and heart rate was 77beats/min. His body weight was 5 kg less than that be-fore the illness began. He was also anuric. Physicalexamination did not reveal any remarkable signs exceptfor redness and purulent discharge at the exit site (Fig. 2A). Laboratory data are shown in Table 1. Fibrin precipi-tation was present in the effluent, but it was not bloody

Table 1 Laboratory data of case 1 and case 2

Case 1 Case 2 Reference range

Blood

White blood cell count (/μL) 3600 11,970 2900–7800

Neutrophil (%) 64.9 95.3 46–62

Hemoglobin (g/dL) 9.4 11.2 10.1–14.7

Platelet count (× 103/μL) 221 179 131–384

Albumin (g/dL) 3.2 1.7 3.9–5.1

Creatinine (mg/dL) 6.4 9.19 0.4–0.8

Blood urea nitrogen (mg/dL) 47 48 8–22

Glucose (mg/dL) 115 137 78–110

Sodium (mEq/L) 136 129 136–144

Potassium (mEq/L) 3.7 2.9 3.6–4.8

Chloride (mEq/L) 100 89 99–109

Calcium (mg/dL) 8.8 7.9 8.5–9.9

Phosphorus (mg/dL) 5.3 3.8 2.6–4.5

C-reactive protein (mg/dL) 0.1 26.6 ≦ 0.2

β-D-Glucan (pg/mL) < 3 < 3 < 11

Dialysis effluent

Nucleated cell count (/μL) 40 160

Neutrophil (%) 2 87

Gram stain Negative Negative Negative

Admission day on which acid-fast bacilli stain was positive Day 18 Day 10

Ono et al. Renal Replacement Therapy (2018) 4:52 Page 3 of 10

(Fig. 2 B). The effluent nucleated cell count was 160cells/μL (87% neutrophils), and a gram stain was nega-tive (Table 1). Blood, sputum, and stool cultures were allnegative. On CT, he showed no focal signs of inflamma-tion except for increased density of the subcutaneous fataround the PD catheter that extended from the exit siteto the entrance into the peritoneal cavity, indicating atunnel infection.He was diagnosed with peritonitis based on the abnor-

mal effluent and tunnel infection detected by CT. Hewas started on intravenous cefazolin and ceftazidimeempirically. Although cefazolin was changed to intraven-ous vancomycin due to ineffectiveness, he had no signsof improvement on the 4th day of admission. The nucle-ated cell count of the effluent increased to 480/μL (62%neutrophils), and the effluent culture was negative forfungus and MRSA. Therefore, on the 5th day of admis-sion, intravenous amikacin and oral clarithromycin werestarted, ceftazidime was discontinued, and PD was chan-ged to HD because of a suspected atypical infection. Onthe 6th day of admission, he showed signs of ileus andwas treated with insertion of a nasogastric tube. CTshowed focal encapsulated ascites in the peritonealcavity and possible EPS. On the 10th day of admission,culture effluent taken on the 4th day of admission wasfound to be AFB-stain positive and was identified as M.abscessus on the 17th day of admission. On the 11th day

of admission, the PD catheter was removed (culture waspositive for M. abscessus), and vancomycin was changedto daily intravenous imipenem/cilastatin according toantimicrobial susceptibility testing on the 17th day ofadmission. After starting imipenem/cilastatin, his condi-tion gradually improved (Fig. 2). Oral food intake wasrecommended on the 23rd day of admission. His bloodtest results and inflammatory reaction improved al-though the encapsulated ascites remained on the 40thday of admission (Fig. 3 B). Daily intravenous imipenem/cilastatin was changed to daily oral moxifloxacin on the59th day of admission in preparation for ambulatorycare. On the 135th day of admission, he was discharged.Daily oral clarithromycin and moxifloxacin and intermit-tent intravenous amikacin at each HD session werecontinued for a total of 6 months, but he developed afever and abdominal pain 16months after the onset ofperitonitis. We performed an abdominal CT and made adiagnosis of ileus due to the enlarged encapsulated asci-tes and dilated intestinal tracts with fluid levels (Fig. 4A–C). The culture of the ascites was positive for Escheri-chia coli, Enterococcus faecium, and Enterococcus avium,but not for M. abscessus. We speculated that multipleintestinal bacteria had inflowed into the encapsulatedascites by intestinal perforation due to EPS, resulting inmicrobial substitution. After he was treated by thedrainage of the encapsulated ascites, stopping oral food

A

B

Fig. 2 The clinical course of case 2. Horizontal axis indicates hospitalization. Line graph indicates the trend in serum C-reactive protein level. Onthe 1st day of admission, the exit site was red with purulent discharge (a). The dialysis effluent on the 1st day of admission had fibrin precipitationwithout blood (b). The PD catheter was removed on the 11th day of admission. The patient was discharged on the 135th day of admission. Thepatient developed encapsulating peritoneal sclerosis 16months after the onset of peritonitis, and he was discharged 20months after the onset ofperitonitis. AMK, amikacin; CAM, clarithromycin; CAZ, ceftazidime; CEZ, cefazolin; CRP, C-reactive protein; EPS, encapsulating peritoneal sclerosis; IPM/CS,imipenem/cilastatin; MFLX, moxifloxacin; SBT/ABPC, sulbactam/ampicillin; VCM, vancomycin

Ono et al. Renal Replacement Therapy (2018) 4:52 Page 4 of 10

intake, and intravenous antibiotics use, the inflammatoryreaction improved and the size of the ascites wasreduced. Leaking oral contrast media into the retainedascites revealed intestinal perforation, however (Fig. 4D). We believe that the infection of the encapsulated as-cites was complicated by intestinal rupture due to EPS.To diminish bowel leakage into the infected cavity, weadded a continuous subcutaneous infusion of octreotide300 μg/24 h for treatment. After 3.5 months of antibiotictreatment and octreotide for 3 weeks, the fistula betweenthe encapsulated ascites and bowel closed, and thepatient was discharged 4 months later.

Mini-review of PD-associated peritonitis by M. abscessusEtiologyPeritonitis by M. abscessus is a rare complication amongPD patients. Including our cases, there are only 18 casesreported in the literature, mostly from Asia, Australia, theNetherlands, and the USA (Table 2) [4–11], as Yang et al.reported previously [5]. NTM infection tends to occur inpatients with immunodeficiency and implanted artificialmaterials. Among patients treated with PD, under-dialysis,poor residual renal function, and a history of broad-spectrum antibiotics use have been reported as risk factors[2, 7, 12]. Recently, topical gentamicin use at the exit site

A B

Fig. 3 Encapsulated ascites detected by computed tomography in both cases. On the 48th day of admission in case 1 with C-reactive protein(CRP) 1.3 mg/dL (a). On the 40th day of admission in case 2 with CRP 3.6mg/dL (b). White arrowheads indicate encapsulated ascites

A B

C D

Fig. 4 Abdominal computed tomography images 16 months after the onset of peritonitis in case 2. Dilated intestinal tracts with fluid levelssuggest ileus (a). It is of note that encapsulated ascites were observed in the right abdomen. Enlarged encapsulated ascites with a drainagecatheter and dilated intestinal tracts in coronal sections (b), in horizontal sections (c). The ascites appear to be adjacent to the dilated intestinaltracts. After drainage, the encapsulated ascites were reduced in size, but oral contrast leaking into the residual encapsulated ascites suggested intestinalperforation (d). White arrows indicate the intestinal tract, white arrowheads indicate the encapsulated ascites, and open white arrowheads indicate thedrainage catheter

Ono et al. Renal Replacement Therapy (2018) 4:52 Page 5 of 10

Table

2Characteristicsandclinicalpresen

tatio

nof

16previouslyrepo

rted

casesandou

rtw

ocases

Case

Cou

ntry

Age

/sex

AFB

test

Daysto

initiateNTM

treatm

entfro

mon

set

Routeof

infection

History

oftopicalG

MPeak

cellcoun

tof

effluen

t(/μL)

Antibiotics(duration)

Cathe

terremoval

Com

plication

Prog

nosis

Ref

1Japan

59/F

(−)

18ESI,TI

(+)

1700

AZM

(1week)

CAM

(22weeks)

AMK(22weeks)

IPM/CS(23weeks)

(+)

Abscess

HD

Case1

2Japan

67/M

(−)

5ESI,TI

(+)

480

CAM

(28weeks)

AMK(28weeks)

IPM/CS(6weeks)

MFLX(20weeks)

(+)

Abscess/EPS

HD

Case2

3Hon

gKo

ng39/F

N/A

N/A

ESI

(+)

N/A

AMK(8weeks)

CAM

(28weeks)

MEPM

(4weeks)

(+)

Abscess

HD

[4]

4Hon

gKo

ng45/M

N/A

N/A

ESI

(+)

N/A

AMK(4weeks)

MFLX(20weeks)

AZM

(6weeks)

(+)

(−)

ResumingPD

[4]

5Taiwan

44/F

(+)

28ESI

(−)

53,512

CAM

(165

days)

AMK(68days)

MEPM

(165

days)

LVFX

(111

days)

(+)

Abscess

Death

[5]

6Taiwan

58/F

(+)

3ESI,TI

(−)

286

IPM/CS(70days)

AMK(50days)

CAM

(234

days)

CPFX(217

days)

DOXY

(180

days)

(+)

Abscess

HD

[5]

7Sing

apore

70/M

(−)

12N/A

(−)

993

MEPM

(N/A)

CAM

(4weeks)

AMK(4weeks)

(+)

Abscess

Death

[6]

8Sing

apore

50/M

(−)

9ESI

(−)

1715

CAM

(12weeks)

CPFX(12weeks)

(+)

(−)

HD

[6]

9Sing

apore

56/M

(−)

10ESI,TI

(−)

115

CAM

(12weeks)

AMK(6weeks)

(+)

(−)

Death

[6]

10Sing

apore

60/F

(+)

7ESI,TI

(−)

146

CAM

(12weeks)

AMK(6weeks)

(+)

(−)

ResumingPD

[6]

11Japan

51/F

(+)

6ESI,TI

(−)

1200

CAM

(7weeks)

CPFX(3weeks)

AMK(3weeks)

(+)

Abscess

HD

[7]

12Saud

iArabia

60/F

(+)

10ESI,TI

(−)

180

CAM

(8weeks)

AMK(8weeks)

(+)

(−)

HD

[8]

13Saud

iArabia

64/F

(+)

6N/A

(−)

214

CAM

(12weeks)

(+)

(−)

HD

[8]

14Australia

49/M

N/A

N/A

N/A

N/A

N/A

CEZ

(N/A)

(+)

EPS

Death

[9]

15Australia

40/F

N/A

N/A

N/A

N/A

N/A

AMK(N/A)

Cefoxitin(N/A)

(+)

(−)

N/A

[9]

Ono et al. Renal Replacement Therapy (2018) 4:52 Page 6 of 10

Table

2Characteristicsandclinicalpresen

tatio

nof

16previouslyrepo

rted

casesandou

rtw

ocases(Con

tinued)

Case

Cou

ntry

Age

/sex

AFB

test

Daysto

initiateNTM

treatm

entfro

mon

set

Routeof

infection

History

oftopicalG

MPeak

cellcoun

tof

effluen

t(/μL)

Antibiotics(duration)

Cathe

terremoval

Com

plication

Prog

nosis

Ref

16Australia

65/M

N/A

N/A

N/A

N/A

N/A

Ticarcillin

(N/A)

VCM

(N/A)

GM

(N/A)

(+)

(−)

N/A

[9]

17TheNethe

rland

s73/F

N/A

34ESI

N/A

N/A

TGC(N/A)

CAM

(N/A)

IPM/CS(N/A)

(+)

(−)

Death

[10]

18USA

67/M

(+)

7N/A

(−)

1647

AMK(12weeks)

CAM

(12weeks)

(+)

(−)

HD

[11]

Thistablewas

basedon

theworkby

Yang

etal.asareference[5].AFB,acid-fast

bacilli,A

MKam

ikacin,A

ZMazith

romycin,C

AM

clarith

romycin,C

EZcefazolin

,CPFXciprofloxacin,

DOXY

doxycycline,

EPSen

capsulating

periton

ealsclerosis,ESIexit-site

infection,

Ffemale,

GM

gentam

icin,H

Dhe

mod

ialysis,IPM/CSim

ipen

em/cilastatin,LVFXlevo

floxacin,

Mmale,

MEPM

merop

enem

,MFLXmoxifloxacin,N

/Ano

tap

plicab

le,N

TMno

ntub

erculous

mycob

acteria

,PDpe

riton

eald

ialysis,Refreferences,TItun

nelinfectio

n,TG

Ctig

ecyclin

e,VC

Mvancom

ycin,w

week

Ono et al. Renal Replacement Therapy (2018) 4:52 Page 7 of 10

has been reported to increase the risk of NTM infection[4]. M. abscessus lives in environments that include water,soil, and dust, and may cause ESI.M. abscessus proliferatingat the exit site might cause peritonitis. The frequency ofESI is high in peritonitis caused by M. abscessus [6]. In pre-vious reports, ESI preceded peritonitis in 10 out of 16 cases(no records in 6 cases), and tunnel infection also precededperitonitis in 5 cases [4–11]. Therefore, ESI by M. abscessustends to spread subcutaneously into the peritoneal cavity ofpatients. Although we could not confirm M. abscessusinfection in the exit site in case 2, the patient’s ESI wastreated by topical gentamicin 6months before the onset ofperitonitis, suggesting that it might increase the risk of M.abscessus infection. Although we only found ESI and noobvious signs of tunnel infection on physical examination,CT scan detected tunnel infection in case 2. Hence, wespeculate that M. abscessus in ESI can spread rapidly intothe abdominal cavity via the catheter tunnel before theemergence of typical signs of tunnel infection commonlyfound by physical examination.As described above, it has been assumed that M. absces-

sus infection spreads from the environment. A recent re-port using next-generation genome sequencing, however,revealed that three substrains of M. abscessus are almostgenetically identical. Moreover, as endemic areas of thesubstrains were close to each other, the authors concludedthat they were clones that had arisen from direct human-to-human transmission [13]. This transmission could occurby infection routes such as cough aerosols by infected pa-tients [13]. Therefore, although there has been no obviousevidence indicating person-to-person transmission, med-ical staff should be aware of this possibility [14].

SymptomsIn comparison to typical bacterial peritonitis, NTM peri-tonitis presents with fewer symptoms, such as abdom-inal pain. In previous reports of a total of 16 cases, therewere 7 cases with abdominal pain, 8 with fever, 3 withdiarrhea, 2 with nausea and vomiting, and 1 with cough(5 cases had no records of symptoms) [4–11]. None ofour patients had severe abdominal pain, although theyhad atypical signs such as malaise and cough.

DiagnosisAccording to the International Society for Peritoneal Dialy-sis Peritonitis Recommendations, peritonitis is generally di-agnosed with clinical features consistent with peritonitisduring PD treatment, such as elevation of the effluent nu-cleated cell count (100 cells/μL with > 50% neutrophils)and positive effluent culture [1]. Among 16 cases in previ-ous reports and our cases of peritonitis with M. abscessus(except for 6 cases without data available), the median ofnucleated effluent cell count was 736.5 cells/μL, althoughin 3 cases, the cell count was only approximately 100 cells/

μL [4–11]. Negative AFB staining in peritonitis caused byNTM is common. Of 12 recorded cases, only 7 hadpositive AFB staining; the positive predictive value was thusonly 58%. The median of the time to initiate specializedtreatment for M. abscessus from the onset of any symp-toms was 9 days, and the longest time was 5 weeks among13 recorded cases [4–11]. Although M. abscessus is classi-fied as a rapidly growing NTM, it requires at least 4 days todetect this organism by culture, whereas bacteria generallyrequire only a few days [2]. As it took 18 days in case 1 and10 days in case 2 to prove a mycobacterium infection, AFBstaining and culture should be performed at the time ofdiagnosis of ESI or tunnel infection. Generally, the myco-bacterial culture tends to be less sensitive than the culturefor common bacteria. Therefore, we should have repeatedlyperformed mycobacterial cultures during treatment in case1 because of the culture-negative refractory exit site andtunnel infection. Furthermore, cultures should beperformed repeatedly, particularly in atypical cases.

TreatmentThere are no current recommendations for the treatmentof peritonitis by M. abscessus. According to the AmericanThoracic Society guidelines of 2007 for pneumonia, M.abscessus is sensitive to clarithromycin, amikacin, cefoxitin,linezolid (limited), and imipenem/cilastatin (limited). Forsevere infection of the skin and soft tissue, the combinationtherapy of clarithromycin (or azithromycin) and others(amikacin, cefoxitin, or imipenem/cilastatin) for more than4months is recommended. For PD, however, removal ofthe PD catheter and debridement are important and prob-ably essential for recovery [15]. In all 16 previous cases, thePD catheters were removed, and ≥ 2 antibiotics were usedfor between 4 and 34 weeks. In addition, clarithromycin,amikacin, and/or imipenem/cilastatin were used in 14 cases[4–11]. In our two cases, the PD catheters were removedand treatment with oral clarithromycin, intravenous imipe-nem/cilastatin (changed to oral moxifloxacin before dis-charge in case 2), and intermittent intravenous amikacinwas continued for a total of 6months, resulting in recoveryfrom ESI, tunnel infection, and peritonitis.

PrognosisThe prognosis of peritonitis caused by M. abscessus hasbeen reported to be poorer than that caused by otherNTM infections [5]. Jiang et al. reported a case of scleros-ing peritonitis 5months after diagnosis of PD peritonitis byM. abscessus, although their description lacked details ofthe clinical course [9]. Ours is the first report to describethe clinical course of EPS occurrence in detail (case 2).Furthermore, the finding that the encapsulated ascitesremained after treatment in case 2 seemed noteworthy.Therefore, we emphasized the risk of M. abscessus-inducedperitonitis developing into EPS, and the possibility of

Ono et al. Renal Replacement Therapy (2018) 4:52 Page 8 of 10

encapsulated ascites as a serious sign for the poor progno-sis of peritonitis such as EPS.

DiscussionWe experienced two cases of M. abscessus-induced peri-tonitis with a history of topical gentamicin use at the exitsites. Although there has been no evidence that M. absces-sus infection can occur at the exit sites as a direct result oftopical gentamicin, frequent use appears to cause microbialsubstitution at the exit sites. It is of note that, in case 2, CTscan detected increased density around the catheter tunnelalthough we could not identify any typical physical findingsindicating skin infection. We speculated that peritonitiscould develop via ESI and tunnel infection. M. abscessuswas reported to be resistant to chlorhexidine and alcohol,which are the most frequently used disinfectants, whereasalcoholic povidone-iodine is effective against it [16, 17].The frequent use of alcoholic povidone-iodine, however,could cause skin injury, which could increase the risk ofESI caused by M. abscessus. Hence, it might be importantto avoid the excessive use of antiseptic solution and to keepthe exit site clean with careful monitoring instead.We emphasize the possibility of EPS after peritonitis by

M. abscessus, particularly with the encapsulated ascitesdetected by CT during treatment. It is not well knownwhether peritonitis caused by M. abscessus contributes toEPS occurrence or not. Evidence from animal experimentsdemonstrates that vascular endothelial growth factor(VEGF) and transforming growth factor-β (TGF-β) canplay crucial roles in the induction of peritoneal fibrosis[18, 19]. Recently, it was reported that serum VEGF levelswere higher in patients with NTM-lung diseases than inpatients with NTM-pulmonary colonization alone. [20]Interestingly, another group reported that serum levels ofcytokines, including TGF-β, in patients with M. abscessusinfection were higher than those in patients without M.abscessus infection [21]. Therefore, peritonitis caused byM. abscessus could carry a high risk of EPS occurrencecompared to peritonitis caused by non-NTM bacteria orother NTMs.

ConclusionsPatients with peritonitis caused by M. abscessus do not al-ways have the typical signs observed in common bacterialperitonitis, such as abdominal pain and elevated effluentnucleated cell count. Therefore, AFB staining and culturefor NTM should be performed at presentation and re-peated until peritonitis by NTM is excluded. Thelong-term use of topical gentamicin may be a possible riskfactor for M. abscessus infection. After diagnosing periton-itis by M. abscessus, empiric treatment with multiple anti-biotics containing clarithromycin, amikacin, andimipenem/cilastatin coupled with the immediate removal

of the PD catheter is strongly recommended. As there isan increased risk of EPS after M. abscessus-induced peri-tonitis, long-term use of antibiotics and careful observationare needed, particularly in cases with remaining encapsu-lated ascites after treatment.

AbbreviationsAFB: Acid-fast bacilli; AMK: Amikacin; AZM: Azithromycin;CAM: Clarithromycin; CAZ: Ceftazidime; CEZ: Cefazolin; CFPM: Cefepime;CPFX: Ciprofloxacin; CRP: C-reactive protein; CT: Computed tomography;DOXY: Doxycycline; EPS: Encapsulating peritoneal sclerosis; ESI: Exit-siteinfection; ESRD: End-stage renal disease; F: Female; GM: Gentamicin;HD: Hemodialysis; IPM/CS: Imipenem/cilastatin; LVFX: Levofloxacin; M: Male;M. abscessus: Mycobacterium abscessus; MEPM: Meropenem;MFLX: Moxifloxacin; MRSA: Methicillin-resistant Staphylococcus aureus; N/A: Not applicable; NTM: Nontuberculous mycobacteria; PD: Peritoneal dialysis;Ref: References; SBT/ABPC: Sulbactam/ampicillin; TA: Tunnel abscess; TAZ/PIPC: Tazobactam/piperacillin; TEIC: Teicoplanin; TGC: Tigecycline; TGF-β: Transforming growth factor-β; VCM: Vancomycin; VEGF: Vascularendothelial growth factor

AcknowledgementsThe authors are grateful to Dr. Keiji Mimura (Kaizuka-Nishide Clinic, Kaizuka,Japan) for his kind support in the treatment of the case 1 patient and A.Yamamoto, S. Ogino, and Y. Mizukami in the Department of Nephrology,Kyoto University Graduate School of Medicine, for their secretarial assistance.

FundingThis work was supported in part by EXT/JSPS KAKENHI Grant Number 17K16079 for writing the manuscript.

Availability of data and materialsAll of the data and materials are included in the manuscript.

Authors’ contributionsEO, EU, and KPM wrote the manuscript. HY, NT, KK, MK, TM, and MYcontributed to the treatment of patients and discussion and reviewed themanuscript. All authors read and approved the final version of themanuscript.

Ethics approval and consent to participateThe case report was written in compliance with the Declaration of Helsinki.

Consent for publicationConsent for publication of this case report was obtained from the patients.

Competing interestsThe authors declare that they have no competing interests.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

Author details1Department of Nephrology, Graduate School of Medicine, Kyoto University,54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. 2MedicalInnovation Center, Graduate School of Medicine, Kyoto University, 53Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. 3Department ofNephrology, Osaka Red Cross Hospital, 5-30 Hudegasaki-cho, Tennoji-ku,Osaka 543-8555, Japan. 4Institute for Clinical and Translational Science, NaraMedical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan.

Received: 28 June 2018 Accepted: 19 November 2018

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